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N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection.

ABSTRACT: The RNA modification N6-methyladenosine (m⁶A) post-transcriptionally regulates RNA function. The cellular machinery that controls m⁶A includes methyltransferases and demethylases that add or remove this modification, as well as m⁶A-binding YTHDF proteins that promote the translation or degradation of m⁶A-modified mRNA. We demonstrate that m⁶A modulates infection by hepatitis C virus (HCV). Depletion of m⁶A methyltransferases or an m⁶A demethylase, respectively, increases or decreases infectious HCV particle production. During HCV infection, YTHDF proteins relocalize to lipid droplets, sites of viral assembly, and their depletion increases infectious viral particles. We further mapped m⁶A sites across the HCV genome and determined that inactivating m⁶A in one viral genomic region increases viral titer without affecting RNA replication. Additional mapping of m⁶A on the RNA genomes of other Flaviviridae, including dengue, Zika, yellow fever, and West Nile virus, identifies conserved regions modified by m⁶A. Altogether, this work identifies m⁶A as a conserved regulatory mark across Flaviviridae genomes.

SUBMITTER: Gokhale NS

PROVIDER: S-EPMC5123813 | biostudies-literature |

REPOSITORIES: biostudies-literature

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N6-methyladenosine in Flaviviridae viral RNA genomes regulates infection

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N6-methyladenosine modification is not a general trait of viral RNA genomes.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-23 | GSE231739 | GEO

N6-methyladenosine modification is not a general trait of viral RNA genomes [Dengue]

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Arabidopsis Messenger RNA N6-methyladenosine Demethylation Regulates Plant Development

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2016-03-24 | E-GEOD-79523 | biostudies-arrayexpress

RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer.

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